Increasing evidence supports the participation of immunologic mechanisms in human neoplastic disease. These mechanisms, primarily of the cellular type, have been demonstrated in a variety of human malignant tumors. In vitro studies by Hellstroms and others have shown that such cell-mediated immunity has a cytotoxic effect on tumor cells and is therefore beneficial to the host. It remains to be seen, however, if and how these mechanisms can be applied to the treatment of cancer. Melanoma is particularly suitable for such clinical studies for several reasons. First Morton and coworkers have demonstrated a common antigen in human melanomas. Secondly, the presence of both cell-mediated and humoral immunity against melanoma cells has been demonstrated by the Hellstroms and Morton, respectively. Also, a good correlation was noted between the clinical state of the disease and the presence of immunity. With this background, we wish to explore the possible treatment of melanoma with transfer factor prepared from lymphocytes of those individuals who have a high degree of cellular immunity against melanoma cells. The classic work of Lawrence has shown that cellular immunity can be transferred in this manner by the transfer factor. The effectiveness of this treatment will be monitored by skin tests to various antigens, in vitro studies (cell inhibition, MIF) on cell-mediated and humoral immunity to cultured melanoma cells and clinical evaluations performed before and after treatment. Also, preliminary studies will be carried out on transfer factor treatment in certain sarcomas and hypernephromas. Another aspect of this project will involve the study of human histocompatibility antigens on the patients' tumor cells, skin fibroblasts and lymphocytes during remission and relapse as well as on lymphocytes of the patients' family members to permit genotyping of the patient. The factors which make this project feasible at our institution include the availability of 1) adequate number of patients, 2) laboratory back-up for tumor immunity studies, and 3) an integrated team approach involving members of both clinical and laboratory departments.